This project investigates the neurobehavioral effects of ingested aluminum (Al). Brain Al accumulation and changes in neurobehavioral indices have been described after dietary exposure to Al in both adult and developing mice. In addition, alterations in tissue Mn and Fe have been documented after developmental but not adult exposure. During the current project period, the behavioral work will be extended to characterize progression/ reversal of effects on neurobehavioral indices (reflexes, activity level, auditory startle) after discontinuation of exposure and possible delayed onset of effects late in the lifespan. In addition, possible deficits in spatial task performance and changes in food motivation suggested by recently completed operant studies will be investigated. Work on brain Al accumulation will involve regional Al localization in the central nervous system (CNS) during development using a guinea pig model. To follow up findings of altered tissue Fe and Mn, developmental indices dependent on these trace elements will be studied. Also, effects of dietary Al on Fe and Mn absorption and tissue distribution will be addressed. As an initial approach to identifying targets of action, CNS cell types (neurons and glia) will be studied in cell culture. These studies will also be designed to determine the biological actions of Al-transferrin (Al-Trf), the predominate Al species in serum, which might be relevant to toxicological effects at the cellular level. Fe and Mn uptake, transferrin receptor number and affinity and transferrin mRNA will be measured in cells exposed to Al-transferrin. Through this work we hope to further clarify potential human health risks associated with ingestion of aluminum in food, water and pharmaceuticals.